RESUMEN
BACKGROUND AND STUDY AIMS: Narrow-band imaging (NBI) has shown promising results in discriminating adenomatous from non-adenomatous colonic polyps. In patients with small polyps (<â10 âmm), the application of NBI within a "resect and discard" strategy, might allow post-polypectomy surveillance intervals to be determined independently from histopathology. The aim of the present study was to assess the feasibility and safety of this approach in routine clinical practice. PATIENTS AND METHODS: Consecutive colonoscopy outpatients with one or more polyps smaller than 10 âmm were prospectively included. Each polyp was categorized by the endoscopist as adenoma or non-adenoma according to simplified NBI criteria, and future post-polypectomy surveillance interval was assigned accordingly. Following histopathology, post-polypectomy surveillance interval was subsequently re-assigned, and the accordance between endoscopy- and histology-directed surveillance strategies was calculated. RESULTS: Among 942 colonoscopy patients, 286 (30.4â%) with only small polyps were included. In total, 511 small polyps were evaluated; 350 (68.5â%) were adenomas and 18 of these (5.1â%) had histologic features of advanced neoplasia. For the in vivo diagnosis of adenoma, NBI sensitivity, specificity, accuracy, and positive and negative likelihood ratios were 94.9â%, 65.8â%, 85.7â%, 2.80, and 0.08, respectively. The endoscopy-directed surveillance strategy was in accordance with the histology-directed strategy in 237 of 286 patients (82.9â%). In 9.8â% and 7.3â% patients, the endoscopy-directed approach would have resulted in early and delayed surveillance, respectively. CONCLUSIONS: The resect and discard strategy seems to be a viable, safe, and cost-effective approach for the management of patients with small polyps. However, caution in the application of the strategy should be advocated for patients with polyps 6â-â9â mm in size and those with right-sided lesions, due to their malignant potential. The study was registered on Clinicaltrials.gov (NCT01462123).
Asunto(s)
Adenoma/diagnóstico , Adenoma/cirugía , Pólipos del Colon/diagnóstico , Pólipos del Colon/cirugía , Colonoscopía , Aumento de la Imagen/métodos , Adenoma/patología , Pólipos del Colon/patología , Diagnóstico Diferencial , Femenino , Hospitales Comunitarios , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
AIM: The aim of the study is to evaluate attention and perception of parents about children's facial aesthetics, the paediatrician's role in early diagnosis of these problems and the areas of the face considered as the most important from an aesthetic point of view. METHODS: The study was carried out collecting 1214 questionnaires at paediatricians waiting room in the North of Italy. RESULTS: Most parents showed attention toward craniofacial deformities of their children and considered the paediatrician's role as very important in early diagnosis. Profile was considered more important than the front view and face's areas felt as the most important were denture, eyes and nose. CONCLUSION: Despite public opinion, adults are concerned not only about the general health and growth of their children, but also about their facial aesthetics. They, in fact, not only judge aesthetics of the whole face, but also discriminate different views and specific areas of the face. They require, for early diagnosis of dentofacial problems, skilled attention from the paediatrician.
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Actitud Frente a la Salud , Anomalías Craneofaciales/psicología , Estética , Cara , Padres/psicología , Adulto , Niño , Preescolar , Anomalías Craneofaciales/diagnóstico , Diagnóstico Precoz , Humanos , Desarrollo Maxilofacial , Persona de Mediana Edad , Evaluación de Necesidades , Pediatría , Relaciones Médico-PacienteAsunto(s)
Amiloidosis/diagnóstico , Endoscopía Capsular/métodos , Enfermedades Gastrointestinales/diagnóstico , Intestino Delgado , Infarto del Miocardio/diagnóstico , Dolor Abdominal/diagnóstico , Dolor Abdominal/etiología , Amiloidosis/patología , Proteína de Bence Jones/orina , Biopsia con Aguja , Análisis Químico de la Sangre , Diagnóstico Diferencial , Ecocardiografía Doppler , Electrocardiografía , Servicio de Urgencia en Hospital , Endoscopía Gastrointestinal/métodos , Enfermedades Gastrointestinales/patología , Humanos , Inmunohistoquímica , Mucosa Intestinal/patología , Masculino , Melena/diagnóstico , Melena/etiología , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
This study concerned a group of ex-workers (372 males and 99 females) from a firm situated in Bergamo (Italy) that ceased its activity at the beginning of the Nineties. From an introductory analysis of the results, we found out that there isn't excess in the death-rate for liver and bile ducts cancers among the males of this group. Among them, for what concerns the other tumoral pathologies, such as leukaemia and stomach tumors, the information allowed to verify an excess of mortality. However, this increase hasn't result statistically significant. On the contrary, it came out that there is an excess of risk for intestine tumors: standardized death-rate of 2.58. In accordance with the information collected, for the future it will be necessary to carefully examine the research in order to verify the existence of a direct connection to the exposure at PCB and study the incidence (not only for mortality) of these neoplasms.
Asunto(s)
Contaminantes Ambientales/efectos adversos , Neoplasias/inducido químicamente , Neoplasias/mortalidad , Enfermedades Profesionales/mortalidad , Bifenilos Policlorados/efectos adversos , Neoplasias de los Conductos Biliares/inducido químicamente , Neoplasias de los Conductos Biliares/epidemiología , Neoplasias de los Conductos Biliares/mortalidad , Femenino , Humanos , Incidencia , Neoplasias Intestinales/inducido químicamente , Neoplasias Intestinales/epidemiología , Neoplasias Intestinales/mortalidad , Italia/epidemiología , Leucemia/inducido químicamente , Leucemia/epidemiología , Leucemia/mortalidad , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/mortalidad , Masculino , Neoplasias/epidemiología , Enfermedades Profesionales/epidemiología , Ocupaciones , Factores Sexuales , Neoplasias Gástricas/inducido químicamente , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/mortalidadRESUMEN
PURPOSE: To assess reproducibility of central corneal thickness (CCT) measurement by means of ultrasonic pachymetry. METHODS: Fifty one volunteers underwent three sessions of CCT measurements, each consisting of three CCT measurements, performed by each of three different observers. Intra- and interobserver reproducibility was calculated by means of intraclass correlation coefficient (ICC). The expected range of variability between two independent evaluations was calculated using scatter plots of each test-retest difference against their mean. The standard deviation of the mean differences in the test-retest scores was used to describe the differences in the score spread. RESULTS: The ICC ranges of the intra- and interobserver evaluations were 0.95-0.97 and 0.89-0.95 respectively; the expected variability was < or = +/-1% and < or = +/- 2% respectively (95% confidence interval). CONCLUSIONS: The measurement of CCT by means of ultrasonic pachymetry is highly reproducible.
Asunto(s)
Córnea/anatomía & histología , Córnea/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Córnea/patología , Técnicas de Diagnóstico Oftalmológico , Glaucoma de Ángulo Abierto/diagnóstico por imagen , Glaucoma de Ángulo Abierto/patología , Humanos , Modelos Lineales , Persona de Mediana Edad , Variaciones Dependientes del Observador , Hipertensión Ocular/diagnóstico por imagen , Hipertensión Ocular/patología , Valores de Referencia , Reproducibilidad de los Resultados , UltrasonografíaRESUMEN
BACKGROUND: There are very few studies in the Italian and international literature concerning occupational diseases and their prevention in the building industry. OBJECTIVES: The aim of this study was risk assessment in the building industry. METHODS: We analyzed the international literature and the results of our cross-sectional study, which involved more than 1000 workers. RESULTS: The analysis of several studies and of our experience suggests a high occupational risk in this field and shows as main risk factors: noise, dusts, fibers, manual lifting, prolonged static positions, repetitive motions, hand-shoulder and whole-body vibrations, chemicals and weather conditions. In addition, non-occupational risk factors can influence health: e.g., habits and lifestyle, like hypercaloric diet, cigarette smoking and alcohol consumption. CONCLUSIONS: Preventive measures and training initiatives are urgently needed to improve the safety and the health among building workers.
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Materiales de Construcción/efectos adversos , Enfermedades Profesionales/epidemiología , Adulto , Femenino , Guías como Asunto , Humanos , Industrias/estadística & datos numéricos , Italia/epidemiología , Estilo de Vida , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/etiología , Medicina del Trabajo/organización & administración , Factores de Riesgo , Administración de la Seguridad/organización & administraciónRESUMEN
Eleven gastrointestinal neoplasms from 10 aged horses and 1 pony were examined grossly, his tologically, immunohistochemically, and (in two cases) ultrastructurally. Clinical signs were associated with two neoplasms, and the other nine tumors were incidental findings at laparotomy or necropsy. The neoplasms were solitary (9/11) or multifocal (2/11), well demarcated, serosal or mural masses of stomach (1), jejunum (1), ileum (3), cecum (5), and/or colon (2). Microscopic examination revealed discrete spindle cells arranged in compact patterns with fascicles and whorls or cribriform pattern with fascicles and rare palisades, often with a myxoid interstitial matrix. Three tumors infiltrated between the muscularis interna and the muscularis externa at the myenteric plexi. All neoplasms were vimentin positive, 3/11 were S-100 positive, 2/11 were muscle actin positive, and no neoplasm was positive for glial fibrillary acid protein, desmin, factor VIII, chromogranin, or neuron-specific enolase. Of the two tumors studied ultrastructurally, one contained an admixture of smooth muscle cells and cells resembling Schwann cells, and the second was populated by homogeneous fusiform mesenchymal cells separated by homogeneous matrix. Gastrointestinal stromal tumors (GIST) have been recognized in humans, more recently in dogs and nonhuman primates, and now in equids. Most of these tumors are comprised of a loosely arranged network of spindled cells separated by myxoid matrix. GIST may be composed of myogenic, neurogenic, combined myogenic and neurogenic, and undifferentiated mesenchymal cells.
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Neoplasias Gastrointestinales/veterinaria , Enfermedades de los Caballos/patología , Animales , Femenino , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/ultraestructura , Caballos , Inmunohistoquímica/veterinaria , Masculino , Microscopía Electrónica/veterinaria , Células del Estroma/patología , Células del Estroma/ultraestructuraRESUMEN
Between 1990 and 1993, 61 outbreaks of contagious bovine pleuropneumonia (CBPP) were reported in Lombardy, Northern Italy. In this study, gross pathological examination was carried out on 3129 slaughtered cattle, 716 of which (22.9%) showed typical CBPP pulmonary lesions. Single or multiple renal infarcts at different stages of development were observed in 88 (12.2%) of these 716 cattle. The kidneys of 77 cattle whose lungs showed typical CBPP lesions and were bacteriologically and immunohistochemically positive for the small colony type of Mycoplasma mycoides subspecies mycoides (M. m. mycoides SC) were selected and submitted to histological, immunohistochemical and bacteriological examination. Histologically, in chronic CBPP cases, infarcts were characterized by fibrosis, calcification of cortical tubules and tubular atrophy, accompanied by the presence of interstitial inflammatory infiltrates composed of lymphocytes, plasma cells and histiocytes. M. m. mycoides SC antigen was detected immunohistochemically in 65 (84.4%) of the 77 kidneys examined. The antigen was detected in the lumen of blood vessels and in glomerular cells. Immunolabelled interstitial cells and tubular epithelial cells were seen in chronic cases only. M. m. mycoides SC was isolated from the kidneys of 12 animals (15.6%) and more frequently in cases with renal infarcts. This study confirms previous observations that demonstrated a renal involvement in cases of CBPP. Moreover, the immunohistochemical results indicated that M. m. mycoides SC antigen was frequently detectable in different renal structures and cells in spontaneous cases of CBPP.
Asunto(s)
Enfermedades de los Bovinos/patología , Enfermedades Renales/veterinaria , Riñón/patología , Mycoplasma mycoides/aislamiento & purificación , Pleuroneumonía Contagiosa/patología , Enfermedad Aguda , Animales , Antígenos Bacterianos/análisis , Bovinos , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Enfermedad Crónica , Brotes de Enfermedades/veterinaria , Femenino , Técnicas para Inmunoenzimas/veterinaria , Infarto/microbiología , Infarto/patología , Italia/epidemiología , Riñón/microbiología , Enfermedades Renales/microbiología , Enfermedades Renales/patología , Masculino , Mycoplasma mycoides/inmunología , Pleuroneumonía Contagiosa/epidemiología , Pleuroneumonía Contagiosa/microbiologíaRESUMEN
A series of 5H-dibenz[b,f]azepine derivatives was prepared and evaluated for binding affinities to muscarinic receptors in vitro. Among them, compound 8 showed a high affinity for human recombinant M2 receptors (Ki=2.6 nm), a low affinity for M4 receptors (39-fold less than for M2 receptors) and a very low affinity for M1 and M3 receptors (119- and 112-fold less than for M2 receptors, respectively). The high M2 selectivity of 8 may be attributed to the olefinic bond of the azepine ring. Functional experiments showed 8 to be a competitive antagonist with high affinity to the cardiac (pA2=7.1) and low affinity to the intestinal muscarinic receptors (IC50=0.54 microM). In vivo experiments confirmed the in vitro M, selectivity of 8. Acetylcholine-induced bradycardia was dose-dependently antagonized in rats after both intravenous and intraduodenal administration of 8. In rats, cholinergic functions mediated by M1 or M3 receptors (salivary secretion, pupil diameter, gastric emptying, intestinal transit time) were not affected by the oral administration of 8 even at doses as high as 30 times the antibradycardic effective dose. Furthermore, 8 had no analgesic activity in mice, indicating poor central nervous system penetration. In dogs, nocturnal bradycardia was dose-dependently inhibited by the oral route with a duration of action of about 24 h. Compound 8 appears to be a promising cardioselective antimuscarinic agent for the treatment of dysfunctions of the cardiac conduction system such as sinus or nodal bradycardia ("sick-sinus syndrome") and atrioventricular block.
Asunto(s)
Benzazepinas/síntesis química , Benzazepinas/farmacología , Corazón/efectos de los fármacos , Antagonistas Muscarínicos/síntesis química , Antagonistas Muscarínicos/farmacología , Receptores Muscarínicos/metabolismo , Animales , Benzazepinas/metabolismo , Barrera Hematoencefálica , Bradicardia/inducido químicamente , Bradicardia/prevención & control , Células CHO , Cricetinae , Perros , Relación Dosis-Respuesta a Droga , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Tránsito Gastrointestinal/efectos de los fármacos , Cobayas , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Humanos , Técnicas In Vitro , Masculino , Ratones , Antagonistas Muscarínicos/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor Muscarínico M1 , Receptor Muscarínico M2 , Receptor Muscarínico M3 , Receptor Muscarínico M4RESUMEN
Ibuprofen (CAS 15687-27-1) is a nonsteroidal antiinflammatory drug endowed with analgesic, antiinflammatory and antipyretic activity. The main side effect of ibuprofen and nonsteroidal antiinflammatory agents is addressed to disturbances of the gastrointestinal tract, like gastric pyrosis, gastric and intestinal damage. A pharmaceutical formulation of ibuprofen in fast melting tablets consisting in gastroprotected microgranules to be ingested without concomitant water intake (Cibalginadue Fast, hereinafter referred to as test) was compared in this trial with a formulation of ibuprofen in tablets (reference) on 18 healthy volunteers in terms of gastrointestinal and general tolerability. Both the formulations are present on the market. The two formulations were administered according to a two-period, two-formulation, two-sequence, cross-over design in repeated dose regimen to steady state with wash-out. The dose was 400 mg (2 strengths) b.i.d. over 7 days. Before, during and after each study period general tolerability was carefully checked from blood/urine biochemical parameters, adverse events experienced and vital signs. The target parameters were the gastric permeability to sucrose and the intestinal permeability to lactulose and mannitol, which were administered orally and assayed in the urine excreted during a 6-h period. Urinary excretion > 0.15% of sucrose and > 0.04 of the lactulose to mannitol ratio are considered expression of increased gastric and intestinal permeability, respectively. Three volunteers treated with the reference showed an increased gastric permeability > 0.15%. Neither other gastric nor intestinal increased permeability was detected. Occult blood in faeces was negative in all the cases. The incidence of adverse effects experienced was higher with the reference (9 volunteers) than with the test (5 volunteers). In details gastric pyrosis was experienced by six volunteers treated with the reference and only by two volunteers treated with the test. The whole tolerability was better with the test formulation than with the reference, even if these differences did not reach any statistically significant degree. The better tolerability of the test was attributed to its gastroprotection.
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Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Ibuprofeno/efectos adversos , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Estudios Cruzados , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Humanos , Ibuprofeno/administración & dosificación , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Lactulosa/metabolismo , Lactulosa/orina , Masculino , Manitol/metabolismo , Manitol/orina , Persona de Mediana Edad , Sangre Oculta , Permeabilidad , Sacarosa/metabolismo , Sacarosa/orinaRESUMEN
This paper describes four cases of canine rhinosporidiosis which occurred in Italy in 1994 and 1995. Four dogs with a history of exposure to the muddy environment of rice fields, developed respiratory signs. Rhinoscopy revealed nasal polypoid lesions with a characteristic gross appearance due to the presence of multiple, tiny, white-yellowish spots representing sporangia filled with spores. In cytological samples obtained by brushing, many spores were present in an inflammatory background. Histologically, the polyps consisted of fibrovascular tissue embedding sporangia in different developmental stages, and free spores which elicited a severe pyogranulomatous inflammation. All the dogs were treated surgically and the condition did not recur in two cases during a year's follow-up and in the other two cases during two years.
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Enfermedades de los Perros/microbiología , Cavidad Nasal/microbiología , Rinosporidiosis/veterinaria , Animales , Enfermedades de los Perros/patología , Enfermedades de los Perros/cirugía , Perros , Europa (Continente) , Femenino , Inflamación , Masculino , Cavidad Nasal/patología , Cavidad Nasal/cirugía , Pólipos/microbiología , Pólipos/veterinaria , Rinosporidiosis/microbiología , Rinosporidiosis/patología , Esporas Fúngicas , Procedimientos Quirúrgicos Operativos/veterinaria , Resultado del TratamientoRESUMEN
Brush cytology was used as a diagnostic aid in 85 cats affected with chronic intranasal disease. Fifty-three of these cases, sampled over a five-year period, were included in this study, while the other cases were excluded due to poor cellularity of the cytological samples (nine cases) or a lack of histological or follow-up data (23 cases). Thirty-six brush samples were classified by cytology as inflammatory. Subsequent histological examination revealed a false negative diagnosis of neoplasia in six cats, two of which had malignant tumours (one adenocarcinoma and one lymphoma), the remaining four having benign tumours (two adenomas and two osteochondromas). Seventeen samples were classified by brush cytology as neoplastic. This was confirmed in 16 of these cases by histology or follow-up (nine epithelial malignant tumours, six lymphomas and one osteosarcoma). In the remaining case, a false positive diagnosis of lymphoma was made. The procedure had an overall 86.8 per cent (46/53) agreement between the diagnosis of inflammatory conditions versus neoplasia, with a sensitivity of 72.7 per cent, a specificity of 96.8 per cent, a predictive value of a positive test of 94.1 per cent and a predictive value of a negative test of 83.3 per cent.
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Enfermedades de los Gatos , Mucosa Nasal/patología , Enfermedades Nasales/veterinaria , Neoplasias Nasales/veterinaria , Animales , Gatos , Enfermedad Crónica , Reacciones Falso Negativas , Femenino , Linfocitos/patología , Linfoma/patología , Linfoma/veterinaria , Masculino , Enfermedades Nasales/patología , Neoplasias Nasales/patología , Manejo de Especímenes/métodos , Manejo de Especímenes/veterinariaRESUMEN
Outbreaks of contagious bovine pleuropneumonia (CBPP) were reported in Lombardy, Northern Italy, at the end of 1990. For the purpose of this study, 54 slaughtered Holstein-Friesian cows showing typical lung lesions of CBPP from which the small colony type of Mycoplasma mycoides subspecies mycoides (M. m. mycoides SC) was isolated, were selected. Thoracic lymph nodes from these animals were sampled for bacteriological, histological and immunohistochemical analysis. Acute, subacute and chronic lesions were observed in 13, 12 and 29 cases, respectively. In the 13 animals showing acute lung lesions, an increased number of macrophages was observed, especially in the subcapsular sinuses, but frequently also in the cortical and medullary sinuses of the thoracic lymph nodes; in all 13 acute cases M. m. mycoides SC antigen was detected immunohistochemically in the cytoplasm of the macrophages. In 10 out of the 12 cases with subacute lung lesions, mycoplasma antigen was observed in macrophages located in sinuses, as well as in those scattered in the lymph node parenchyma. Hyperplasia of germinal centres in follicles was observed histologically in most of the 29 cases with chronic lung lesions. In immunohistochemically labelled sections, the characteristic finding observed in 27 of the chronic cases, was the presence of a variable amount of positive material in the germinal centres. These findings demonstrate the involvement of thoracic lymph nodes in CBPP.
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Enfermedades de los Bovinos/patología , Ganglios Linfáticos/patología , Pleuroneumonía Contagiosa/patología , Animales , Bovinos/microbiología , Enfermedades de los Bovinos/microbiología , Femenino , Inmunohistoquímica , Ganglios Linfáticos/microbiología , Mycoplasma mycoides/aislamiento & purificación , Pleuroneumonía Contagiosa/microbiologíaRESUMEN
Recent pulmonary lesions at slaughter in bovines affected by Mycoplasma mycoides during the years 1990-1993 in Northern Italy are reported. Several histologic and immunocytochemical examinations showed that: the earliest lesions of CBPP are foci of desquamative bronchiolo-alveolitis, the highest concentration of the antigen is found in the cytoplasm of desquamated alveolar macrophages. From our results, we can exclude that CBPP begins with interstitial lesions as some authors have hypothesized. On the contrary, the hypothesis, formulated at the beginning of the century, that CBPP begins with a desquamative bronchiolo-alveolitis seems to be more convincing. Our results give some help to construct a correct pathogenesis of the disease.
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Pulmón/patología , Mycoplasma mycoides , Pleuroneumonía Contagiosa/patología , Animales , Antígenos Bacterianos/análisis , Bovinos , Inmunohistoquímica , Italia , Pulmón/microbiología , Mycoplasma mycoides/inmunología , Mycoplasma mycoides/aislamiento & purificaciónRESUMEN
Fifty-two cases of gastrointestinal mucosal tumours of the dog were examined for argyrophil cells by means of the Grimelius stain. Argyrophil cells were found in each of five cases (100 per cent) of gastric adenoma, in five (71.4 per cent) of seven large-intestine adenomas, in 13 (59.1 per cent) of 22 gastric carcinomas, in five (62.5 per cent) of eight small-intestine carcinomas and in four (40 per cent) of ten large-intestine carcinomas. The argyrophil cells represented a minority of the tumour cell population in all cases. These results demonstrate that a significant proportion of gastrointestinal mucosal tumours of the dog contain a mixture of epithelial and endocrine cells. Similar findings have been reported in man.
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Enfermedades de los Perros/patología , Células Enterocromafines/patología , Neoplasias Gastrointestinales/veterinaria , Mucosa Intestinal/patología , Adenoma/patología , Adenoma/veterinaria , Animales , Carcinoma/patología , Carcinoma/veterinaria , Gránulos Citoplasmáticos/ultraestructura , Perros , Neoplasias Gastrointestinales/patología , Nitrato de Plata , Tinción con Nitrato de PlataRESUMEN
Two sublines of the ovarian reticular cell sarcoma M5 in C57BL mice respond differently to cyclophosphamide and other alkylating agents. The subline R16, which is resistant to cyclophosphamide, was obtained by treating M5 mice repeatedly with this compound and subsequently transplanting the regrowing tumor for 16 passages. The R16 subline shows biological characteristics perfectly superimposable to those of the parent line and histologically resembles an undifferentiated mesenchymal neoplasia with numerous atypical nuclei and karyokinetic figures with large necrotic areas. The cytogenetic examination of the distribution in the chromosomal number of R16 indicates that this subline may be considered a clone of the parent line with a modal class of 35 chromosomes (34-37) versus a class of 34 (31-37) in the M5 tumor line. The presence of metacentric chromosomes characterizes the modal class of the two lines, 23 in the R16, and 25 in the M5 tumor lines.
RESUMEN
The antitumor activity of mafosfamide (MFA), and its parent compound cyclophosphamide (CTX), was investigated against an ovarian reticular cell sarcoma growing i.m. in C57BI/6 mice (M5), which is very sensitive to CTX, and against a subline of this tumor (R16) resistant to CTX. MFA is the prototype of a class of oxazaphosphorines which do not require metabolic activation since under physiologic conditions they undergo rapid spontaneous hydrolyzation to the activated 4-hydroxyoxazaphosphorine and retain a spectrum of activity very similar to the parent compound. After a single dose (300 mg/kg X 1) or repeated low doses (100 mg/kg X 6) the antitumoral activity of MFA on the M5 tumor appeared comparable to or only slightly lower than CTX; the highest T/C value for median survival times was 167% in MFA-treated mice vs. 176% in the CTX group. MFA showed no activity against the R16 subline, thus indicating cross-resistance between the two drugs. Marked thickening of the glissonian capsule with compression of the lobular area of the liver, observed on i.p. administration of MFA, did not result in histopathologic abnormalities of the hepatic parenchyma. The therapeutic efficacy of MFA was similar with i.p. and the i.v. route. MFA may represent a good candidate to replace CTX in cases in which a compound acting per se, and not through metabolites, is preferred.